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2
Departments of
*
Biochemistry,
Nutritional Sciences and
**
Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin-Madison, Madison, WI 53706, and
Department of Home Economics, Korea University, Seoul, Korea
2To whom correspondence should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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2 (PPAR2) and CCAAT enhancer
binding protein 
(C/EBP), remained elevated. Cells treated with
trans-10,cis-12 CLA exhibited smaller
lipid droplets, with reduced levels of the major monounsaturated fatty
acids, palmitoleate and oleate. By contrast, the
cis-9,trans-11 isomer did not alter
adipocyte gene expression. Repression of the stearoyl-CoA
desaturase gene expression in adipocytes by the
trans-10,cis-12 isomer may contribute to
the mechanisms by which CLA reduces body fat in mice.
KEY WORDS: • mouse adipocytes • differentiation • conjugated linoleic acid.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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and 1990
, Ip et al. 1991
and 1994
) and reduces atherosclerosis in rabbits
(Lee et al. 1994
). It reduces body fat and enhances lean
body mass in mice and pigs (Dugan et al. 1997
,
Park et al. 1997
), an activity that is attributed to the
trans-10,cis-12 CLA isomer (Park et al. 1999b
). Adding trans-10,cis-12 CLA to the
culture medium of mouse 3T3-L1 adipocytes produces a dose-dependent
reduction in lipoprotein lipase activity, and apparently induces
lipolysis as well in this cell line (Park et al. 1999b
).
CLA also normalizes the impaired glucose tolerance of Zucker diabetic
fatty fa/fa rats (Houseknecht et al. 1998
).
The mechanisms by which CLA exerts these biological effects have not
been completely elucidated. However, one of the effects of CLA that has
been observed consistently is its ability to alter the fatty acid
composition of tissues by reducing the levels of monounsaturated fatty
acids (Lee et al. 1995
). The main monounsaturated fatty
acids, oleate and palmitoleate, are synthesized by the stearoyl-CoA
desaturase (SCD) from stearate and palmitate, respectively.
Palmitoleate and oleate are the major (58%) monounsaturated fatty
acids of membrane phospholipids and triglycerides found in
differentiated 3T3-L1 adipocytes and in mouse adipose tissue in vivo
(Kasturi and Joshi 1982
). A proper ratio of saturated to
monounsaturated fatty acids is important in maintaining membrane
fluidity; alteration of this ratio can influence a variety of
physiologic responses, including adiposity (Field et al. 1990
), metabolic rate (Storlien et al. 1991
) and
insulin sensitivity (Jones et al. 1996
), all of which
are influenced by CLA.
In this study, we used the well-characterized mouse 3T3-L1
preadipocyte cell line as a model of differentiation and lipid
biogenesis to examine the effects of the
cis-9,trans-11 and
trans-10,cis-12 isomers of CLA on adipocyte gene
expression and fat composition. The results demonstrate that treatment
of 3T3-L1 cells with the trans-10,cis-12 isomer
of CLA reduces the expression of the SCD1 in a dose-dependent
fashion (10–100 µmol/L), whereas those of other adipocyte
genes such as adipose P2 (aP2), SCD2, fatty acid synthase (FAS), CCAAT
enhancer binding protein (C/EBP) and peroxisome
proliferator-activated receptor 2 (PPAR2) are not
significantly affected. The downregulation of the SCD1 gene corresponds
to a decrease in SCD protein and enzyme activity as well as in the
total composition of 16:1 and 18:1 fatty acids. We hypothesize that the
trans-10,cis-12 isomer of CLA reduces body fat in
part by decreasing the major monounsaturated fatty acids of
triglycerides, resulting in the formation of small lipid droplets and
small fat cells.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Conjugated linoleic acid (96.6% pure) was prepared as described
(Chin et al. 1992
) and contained 47.6%
trans-10,cis-12; 45.7%
cis-9,trans-11; 1.71%
trans-9,trans-11/trans-10,trans-12
and 3.04% other isomers. The
trans-10,cis-12 and the
cis-9,trans-11 CLA isomers (>95% pure)
were gifts from Dr. Sih of the Department of Pharmacology, University
of Wisconsin-Madison. Methylisobutylxanthine was obtained from
Aldrich (Milwaukee, WI). Dexamethasone and fatty acid methyl standards
were purchased from Sigma Chemical (St. Louis, MO). Fetal bovine serum,
Dulbecco’s modified Eagle’s medium (DMEM), penicillin/streptomycin
and trypsin were from Gibco (Gaithesburg, MD). Insulin was from Eli
Lilly (Indianapolis IN). Calf serum was from Bio Whittaker
(Walkersville, MD). Radionucleotides were from NEN Life Sciences
(Boston, MA).
Cell culture.
3T3-L1 preadipocytes were maintained and induced to differentiate as
described (Bernlohr et al. 1985
). CLA,
trans-10,cis-12, or
cis-9,trans-11 isomers were complexed
with albumin as described previously (Lee et al. 1998
).
The fatty acids were replenished with every medium change unless
otherwise stated. Controls were conducted with albumin in the culture
medium where appropriate.
Oil Red O staining of cultured cells.
Cells were washed with distilled water, fixed with 10% buffered neutral formalin, rinsed again with water, and finally with 70% ethanol. Cells were stained with 10 mL of Oil Red O (0.3%) for 7 min. The dye was washed off with 70% ethanol and then water. Cells were photographed at 100X under light microscopy.
Isolation and analysis of RNA.
Northern analysis was performed with total cellular RNA isolated from
3T3-L1 cells as described (Bernlohr et al. 1985
). After
agarose-formaldehyde gel electrophoresis, the blot was hybridized
with 32P-labeled SCD1, SCD2, aP2, FAS, PPAR2 and
C/EBP cDNAs. pAL15 cDNA was used as the internal loading control.
Western blotting.
Monolayers of preadipocytes or adipocytes were washed with PBS and lysed in 50 mmol/L Tris-HCl, 150 mmol/L NaCl, 1 mmol/L EDTA, 1% NP-40, 0.25% sodium deoxycholate, 0.1% SDS, 1 mmol/L Na3VO4, 10 mmol/L NaMo, 40 mmol/L NaF, 1 mmol/L phenylmethylsulfonyl fluoride, 2 g/L aprotinin and 1 g/L leupeptin. The cell lysates were passed through a 23-gauge needle, incubated at 4°C for 10 min and then centrifuged at 10,000 x g for 10 min at 4°C. Protein concentrations were determined by dye binding assay using bovine serum albumin as the standard. Equal amounts of protein were separated by 10% SDS-PAGE, transferred and immobilized on Immobilon-P transfer membranes (Millipore, Danvers, MA) at 4°C. After blocking with 10% nonfat dry milk in PBS at room temperature for 2 h, the membranes were washed and incubated with rabbit anti-rat SCD as the primary antibody and goat anti-rabbit immunoglobulin G-HRP conjugate as the secondary antibody. Visualization of the SCD protein was performed with the ECL Western blot detection system (Amersham-Pharmacia Biotech, Piscataway, NJ) using procedures provided by the manufacturer.
Measurement of SCD enzyme activity.
The SCD activity was determined as described (Legrand and Bensadoun 1991
). The assay system contained 7.2 mmol/L ATP,
0.54 mmol/L CoA, 6 mmol/L MgCl2, 0.8 mmol/L NADH, 0.1 mol/L
PBS (pH 7.16), 200 nmol of [1-14C]-palmitic acid
(specific activity 0.98 Bq/mol) in 5 µL ethanol, and
microsomal fraction (1.0–1.8 mg protein) in 1 mL final volume.
The reaction was initiated by addition of the microsomal fraction;
incubation was at 37°C for 15 min. The reaction was stopped by adding
1 mL 12% KOH in ethanol, followed by heating for 1 h at 80°C.
Fatty acids were extracted with hexane after acidification with HCl.
Fatty acid methyl esters (FAME) were prepared with 4% HCl/methanol at
60°C for 20 min and separated by TLC on silver nitrate–impregnated
silica gel G plates using a hexane/ether (9:1) solvent system. To help
visualization, cold standards (palmitic and palmitoleic acid methyl
esters) were cospotted with samples. Spots were identified under UV
light after spraying with 0.2% dichlorofluorescein ethanolic solution
and comparison with authentic standards; they were scraped off the
plates, extracted with hexane and subjected to liquid scintillation
counting (Beckman Liqid Scintillation Systems, model LS 5801, Beckman
Instruments, Irvine, CA) using Bio-Safe II. Enzyme activities were
calculated as nanomoles palmitic acid converted to palmitoleic acid per
minute per milligram protein.
Lipid analysis.
Cells were washed twice with cold PBS. Total cellular lipids were extracted three times with 2 mL of chloroform/methanol (2:1 v/v). Aliquots of the lipid extracts were dried under nitrogen, converted to FAME using 4% HCl/methanol at 60°C for 20 min and identified by comparison with standards (Sigma Chemical) by gas chromatography (GC). GC was conducted with a Hewlett-Packard 5890 series II fitted with a flame ionization detector and 3396A integrator. A Supelcowax-10 fused silica capillary column (60 m x 0.32 mm i.d., 0.25 µm film thickness; Bellefonte, PA) was used and oven temperature was programmed from 50 to 200°C, increased 20°C/min, held for 50 min, increased 10°C/min to 220°C, and held for 30 min.
Statistical analysis.
Data in Figure 4 were tested using ANOVA and Duncan’s multiple
range procedure with the Statistics Analysis System (SAS Institute,
Cary, NC). Differences were considered significant when
P 
0.1. One-way ANOVA and Tukey’s multiple
range test were performed on data in Table 1
. Differences were considered significant at P < 0.01.
Values are presented as means ± SEM.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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2, are shown in Figure 1
. In preadipocytes maintained in DMEM (lane 1), the levels of SCD1, aP2
and PPAR2 mRNA were very low but were increased dramatically when
the cells were induced to differentiate with
1-methyl-3-isobutylxanthine, dexamethasone and insulin (MDI) (lane 2).
Continuous treatment of the cells with CLA decreased SCD1, aP2 and
PPAR2 mRNA in a dose-dependent manner (lanes 3–5). The decrease
in aP2 and PPAR2 expression by CLA during 3T3-L1 preadipocyte
differentiation is in agreement with published data (Brodie et al. 1999
). Lanes 6 and 7 (Fig. 1)
show that although there was
little effect by cis-9,trans-11 CLA on SCD1 mRNA,
the trans-10,cis-12 CLA isomer caused a nearly
complete repression of SCD1 mRNA expression similar to the CLA mixture.
aP2 and PPAR2 mRNA levels remained elevated.
Trans-10,cis-12-supplemented plates showed little
Oil Red O staining compared with plates treated with MDI alone or MDI
plus cis-9,trans-11 CLA isomer (Fig. 1B
), indicating that in addition to repressing the SCD1 gene
expression, the trans-10,cis-12 isomer reduced
accumulation of lipid droplets during the differentiation of the 3T3-L1
preadipocytes. We determined the dose response for
trans-10,cis-12 isomer on SCD1 mRNA expression.
SCD1 mRNA was decreased in a dose-dependent manner with the
addition of 10–100 µmol/L
trans-10,cis-12. The
trans-10,cis-12 (100 µmol/L) isomer
caused a > 90% decrease in SCD1 mRNA compared with
MDI-treated cells (Fig. 2
). Lower concentrations were less effective in a dose-dependent
manner [median effective dose (ED50) = 10
µmol/L]. The expression of PPAR2 and C/EBP mRNA was
not decreased with the addition of 10–100 µmol/L
trans-10,cis-12.
|
|
, lane 1). Upon addition of MDI (lane 2), there was a substantial
increase in cross-reacting SCD protein. The protein levels were
decreased in a dose-dependent manner in cells treated with CLA
(lanes 3–5). The cis-9,trans-11 CLA had no
significant effect on the level of the SCD protein (lane 6). However,
in the presence of trans-10,cis-12 CLA (lane 7),
the 37-kDa SCD protein (Heinemann and Ozols 1998
) was
detectable but strongly repressed.
|
. The SCD activity was reduced by 60% compared with the
MDI-differentiated cells by the
trans-10,cis-12 isomer, whereas the
cis-9,trans-11 isomer reduced the activity only
by 15% (P 0.1). Fatty acid analysis showed that cells
differentiated in the presence of trans-10,cis-12
CLA contained significantly lower palmitoleic (16:1) and oleic (18:1)
acids compared with cells differentiated with MDI (Table 1)
. The ratios
of 16:1 to 16:0, and 18:1 to 18:0 (desaturation index) were higher in
MDI-differentiated cells than in cells treated with
trans-10,cis-12 CLA. The decrease in levels of
monounsaturated fatty acids and the desaturation index indicates a
decrease in SCD activity.
|
shows that trans-10,cis-12 reduced the expression
of the SCD1 mRNA during the course of differentiation. The expression
of the SCD2, aP2, PPAR2 and FAS mRNAs was reduced only slightly by
trans-10,cis-12 CLA. The expression of pAL15 cDNA
used as a control was not altered in the presence of MDI, or MDI plus
trans-10,cis-12. The presence of SCD2, aP2,
PPAR2 and FAS transcripts suggests that the levels of
trans-10,cis-12 CLA isomer used did not
completely block preadipocyte differentiation.
|
|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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reported that CLA inhibited
differentiation and repressed adipocyte gene expression during the in
vitro differentiation of mouse 3T3-L1 preadipocytes into adipocytes.
Park et al. (1999a)
provided evidence indicating that
dietary CLA does not induce, and may have suppressed adipocyte
differentiation in mice. Both of these observations are consistent with
the data presented in Figure 1
(lanes 3–5).
By contrast, other laboratories (Houseknect et al. 1998
,
Satory and Smith 1999
) have reported that CLA may
enhance preadipocyte differentiation in vitro under some conditions,
possibly by mimicking the effects of thiazolidinediones via activation
of PPAR2. However, the available in vivo data (Park et al. 1999a
) are not consistent with this hypothesis. The reasons for
the discrepancies are not clear, but the use of CLA preparations
containing different amounts and ratios of CLA isomers should be
considered. For example, some commercial CLA preparations are poorly
characterized and contain numerous CLA isomers; this may complicate
data interpretation (Pariza. et. al. 2000
, Sehat et al. 1999
). However, the CLA preparations that we have
utilized in this study are virtually pure single isomers and fully
characterized isomer mixtures prepared by our published methods.
Our results show that the trans-10,cis-12 CLA
isomer elicits some but not all of the in vitro effects of the CLA
isomer mixture. Notably, the trans-10,cis-12 CLA
isomer decreased SCD1 mRNA expression, protein level and enzyme
activity during the differentiation of 3T3-L1 preadipocytes (Figs. 1
2
3
4
5)
. Consistent with this effect, the levels of 16:1 and 18:1 fatty
acids were also reduced (Table 1)
. Bretillon et al. (1999)
reported that trans-10,cis-12 CLA
specifically inhibited SCD activity, whereas the
cis-9,trans-11 CLA isomer was without such
effect, a finding that we have confirmed (unpublished) previously. We
reported previously that the trans-10,cis-12 CLA
isomer also specifically reduced lipoprotein lipase activity and the
amount of triglycerides and glycerol in 3T3-L1 cells (Park et al. 1999b
). The reduction of lipid within 3T3-L1 adipocytes
induced by trans-10,cis-12 CLA (Fig. 1)
may be
related in part to the inhibition of the SCD gene because 16:1 and 18:1
monounsaturated fatty acids constitute 58% of the fatty acids in fat
droplets of these cells (Lee et al. 1995
). This finding
supports the hypothesis that this isomer may block 3T3-L1 preadipocyte
differentiation. However, the lack of effect of the
trans-10,cis-12 CLA isomer on the expression of
aP2 and PPAR2 (Fig. 1)
argues against this interpretation. Our
results are consistent with the conclusion that
trans-10,cis-12 CLA does not block adipocyte
differentiation per se but rather specifically inhibits the expression
of the SCD gene, resulting in reduced accumulation of oleic and
palmitoleic acids and hence fat cells with small lipid droplets.
We cannot yet explain why the CLA isomer mixture reduced aP2 and
PPAR2 mRNA, whereas the trans-10,cis-12 CLA
isomer was without such effect (Fig. 1)
. It is possible that the effect
is caused by another CLA isomer that is present in the CLA mixture but
not in the pure trans-10,cis-12 CLA isomer
preparation. We think that this is unlikely, however, on the basis of
our previous work in the 3T3-L1 system with preparations containing
various CLA isomer ratios (Park et al. 1999b
). However,
the CLA isomer mixture also contains unreacted linoleic acid, which by
itself blocks 3T3-L1 preadipocyte differentiation and adipocyte gene
expression (Casimir and Ntambi 1996
). The other
possibility that has not been tested is that certain physiologic
effects of CLA require interaction of the major CLA isomers, and yet
the individual isomers may also exert different physiologic effects.
The trans-10,cis-12 isomer of CLA displays other
biological activities that are associated with lipid metabolism. For
example, mature cultured 3T3-L1 adipocytes treated with
trans-10,cis-12 CLA exhibit reduced lipoprotein
lipase activity and reduced intracellular concentrations of
triglyceride and glycerol (Park et al. 1999b
). These
actions, coupled with the activities that we now report, may explain
the reduction of body fat in mice by CLA isomer mixtures that contain
trans-10,cis-12 CLA (Park et al. 1997
) as well as by purified preparations of the
trans-10,cis-12 CLA isomer (Park et al. 1999b
)
The mechanism of trans-10,cis-12 action on SCD
gene expression could involve decreased SCD mRNA stability
and/or gene transcription. We showed previously that
polyunsaturated fatty acids such as linoleic acid repress the
expression of the SCD gene in adipocytes at the level of mRNA stability
(Sessler et al. 1996
). Determing whether CLA decreases
the expression of the SCD gene by reducing mRNA stability requires
further investigation.
|
ACKNOWLEDGMENTS |
|---|
2 cDNA probe and Julis Ozols (University of Connecticut
Health Center, Farmington, CT) for the antibody to the rat liver
microsome stearoyl-CoA desaturase. We thank Jayne M. Storkson for
technical assistance. |
FOOTNOTES |
|---|
3 Abbreviations used: aP2, adipose P 2; C/EBP, CCAAT enhancer binding protein ; CLA, conjugated linoleic acid; DMEM, Dulbecco’s essential Eagle’s medium; FAME, fatty acid methyl esters; FAS, fatty acid synthase; GC, gas chromatography; MDI, 1-methyl-3-isobutylxathine, dexamethasone and insulin; PPAR2, peroxisome proliferator-activated receptor 2; SCD, stearoyl-CoA desaturase.
Manuscript received November 15, 1999. Initial review completed December 24, 1999. Revision accepted April 3, 2000.
|
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 U. Riserus, G. D. Tan, B. A. Fielding, M. J. Neville, J. Currie, D. B. Savage, V. K. Chatterjee, K. N. Frayn, S. O'Rahilly, and F. Karpe Rosiglitazone Increases Indexes of Stearoyl-CoA Desaturase Activity in Humans: Link to Insulin Sensitization and the Role of Dominant-Negative Mutation in Peroxisome Proliferator-Activated Receptor-{gamma} Diabetes, May 1, 2005; 54(5): 1379 - 1384. [Abstract] [Full Text] [PDF]
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A. Bhattacharya, Md. M. Rahman, D. Sun, R. Lawrence, W. Mejia, R. McCarter, M. O'Shea, and G. Fernandes The Combination of Dietary Conjugated Linoleic Acid and Treadmill Exercise Lowers Gain in Body Fat Mass and Enhances Lean Body Mass in High Fat-Fed Male Balb/C Mice J. Nutr., May 1, 2005; 135(5): 1124 - 1130. [Abstract] [Full Text] [PDF]
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D. L. Palmquist, N. St-Pierre, and K. E. McClure Tissue Fatty Acid Profiles Can Be Used to Quantify Endogenous Rumenic Acid Synthesis in Lambs J. Nutr., September 1, 2004; 134(9): 2407 - 2414. [Abstract] [Full Text] [PDF]
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 Y. Wang and P. J. Jones Dietary conjugated linoleic acid and body composition Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1153S - 1158S. [Abstract] [Full Text] [PDF]
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R. S McLeod, A. M LeBlanc, M. A Langille, P. L Mitchell, and D. L Currie Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density lipoprotein metabolism Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1169S - 1174S. [Abstract] [Full Text] [PDF]
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 Y. Wang, B. Kurdi-Haidar, and J. F. Oram LXR-mediated activation of macrophage stearoyl-CoA desaturase generates unsaturated fatty acids that destabilize ABCA1 J. Lipid Res., May 1, 2004; 45(5): 972 - 980. [Abstract] [Full Text] [PDF]
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G. C. Burdge, B. Lupoli, J. J. Russell, S. Tricon, S. Kew, T. Banerjee, K. J. Shingfield, D. E. Beever, R. F. Grimble, C. M. Williams, et al. Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men J. Lipid Res., April 1, 2004; 45(4): 736 - 741. [Abstract] [Full Text] [PDF]
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V. Bontempo, D. Sciannimanico, G. Pastorelli, R. Rossi, F. Rosi, and C. Corino Dietary Conjugated Linoleic Acid Positively Affects Immunologic Variables in Lactating Sows and Piglets J. Nutr., April 1, 2004; 134(4): 817 - 824. [Abstract] [Full Text] [PDF]
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T. M. Larsen, S. Toubro, and A. Astrup Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies J. Lipid Res., December 1, 2003; 44(12): 2234 - 2241. [Abstract] [Full Text] [PDF]
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J. M. Brown and M. K. McIntosh Conjugated Linoleic Acid in Humans: Regulation of Adiposity and Insulin Sensitivity J. Nutr., October 1, 2003; 133(10): 3041 - 3046. [Abstract] [Full Text] [PDF]
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C. Corino, S. Magni, G. Pastorelli, R. Rossi, and J. Mourot Effect of conjugated linoleic acid on meat quality, lipid metabolism, and sensory characteristics of dry-cured hams from heavy pigs J Anim Sci, September 1, 2003; 81(9): 2219 - 2229. [Abstract] [Full Text] [PDF]
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L. Granlund, L. K. Juvet, J. I. Pedersen, and H. I. Nebb Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR{gamma} modulator J. Lipid Res., August 1, 2003; 44(8): 1441 - 1452. [Abstract] [Full Text] [PDF]
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J. A. Kelsey, B. A. Corl, R. J. Collier, and D. E. Bauman The Effect of Breed, Parity, and Stage of Lactation on Conjugated Linoleic Acid (CLA) in Milk Fat from Dairy Cows J Dairy Sci, August 1, 2003; 86(8): 2588 - 2597. [Abstract] [Full Text] [PDF]
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J. M. Brown, M. S. Boysen, S. S. Jensen, R. F. Morrison, J. Storkson, R. Lea-Currie, M. Pariza, S. Mandrup, and M. K. McIntosh Isomer-specific regulation of metabolism and PPAR{gamma} signaling by CLA in human preadipocytes J. Lipid Res., July 1, 2003; 44(7): 1287 - 1300. [Abstract] [Full Text] [PDF]
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X. Xu, J. Storkson, S. Kim, K. Sugimoto, Y. Park, and M. W. Pariza Short-Term Intake of Conjugated Linoleic Acid Inhibits Lipoprotein Lipase and Glucose Metabolism but Does Not Enhance Lipolysis in Mouse Adipose Tissue J. Nutr., March 1, 2003; 133(3): 663 - 667. [Abstract] [Full Text] [PDF]
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M. Yamasaki, H. Chujo, A. Hirao, N. Koyanagi, T. Okamoto, N. Tojo, A. Oishi, T. Iwata, Y. Yamauchi-Sato, T. Yamamoto, et al. Immunoglobulin and Cytokine Production from Spleen Lymphocytes Is Modulated in C57BL/6J Mice by Dietary Cis-9, Trans-11 and Trans-10, Cis-12 Conjugated Linoleic Acid J. Nutr., March 1, 2003; 133(3): 784 - 788. [Abstract] [Full Text] [PDF]
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M. A. Belury, A. Mahon, and S. Banni The Conjugated Linoleic Acid (CLA) Isomer, t10c12-CLA, Is Inversely Associated with Changes in Body Weight and Serum Leptin in Subjects with Type 2 Diabetes Mellitus J. Nutr., January 1, 2003; 133(1): 257S - 260. [Abstract] [Full Text] [PDF]
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M. Miyazaki, F. E. Gomez, and J. M. Ntambi Lack of stearoyl-CoA desaturase-1 function induces a palmitoyl-CoA {Delta}6 desaturase and represses the stearoyl-CoA desaturase-3 gene in the preputial glands of the mouse J. Lipid Res., December 1, 2002; 43(12): 2146 - 2154. [Abstract] [Full Text] [PDF]
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S. R. Demaree, C. D. Gilbert, H. J. Mersmann, and S. B. Smith Conjugated Linoleic Acid Differentially Modifies Fatty Acid Composition in Subcellular Fractions of Muscle and Adipose Tissue but Not Adiposity of Postweanling Pigs J. Nutr., November 1, 2002; 132(11): 3272 - 3279. [Abstract] [Full Text] [PDF]
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L. H. Baumgard, E. Matitashvili, B. A. Corl, D. A. Dwyer, and D. E. Bauman trans-10, cis-12 Conjugated Linoleic Acid Decreases Lipogenic Rates and Expression of Genes Involved in Milk Lipid Synthesis in Dairy Cows J Dairy Sci, September 1, 2002; 85(9): 2155 - 2163. [Abstract] [Full Text] [PDF]
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D. G. Peterson, J. A. Kelsey, and D. E. Bauman Analysis of Variation in cis-9, trans-11 Conjugated Linoleic Acid (CLA) in Milk Fat of Dairy Cows J Dairy Sci, September 1, 2002; 85(9): 2164 - 2172. [Abstract] [Full Text] [PDF]
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S. B. Smith, T. S. Hively, G. M. Cortese, J. J. Han, K. Y. Chung, P. Castenada, C. D. Gilbert, V. L. Adams, and H. J. Mersmann Conjugated linoleic acid depresses the {delta}9 desaturase index and stearoyl coenzyme A desaturase enzyme activity in porcine subcutaneous adipose tissue J Anim Sci, August 1, 2002; 80(8): 2110 - 2115. [Abstract] [Full Text] [PDF]
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K. Eder, N. Slomma, and K. Becker Trans-10,cis-12 Conjugated Linoleic Acid Suppresses the Desaturation of Linoleic and {alpha}-Linolenic Acids in HepG2 Cells J. Nutr., June 1, 2002; 132(6): 1115 - 1121. [Abstract] [Full Text] [PDF]
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M. Evans, X. Lin, J. Odle, and M. McIntosh Trans-10, Cis-12 Conjugated Linoleic Acid Increases Fatty Acid Oxidation in 3T3-L1 Preadipocytes J. Nutr., March 1, 2002; 132(3): 450 - 455. [Abstract] [Full Text] [PDF]
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S. P. Poulos, M. Sisk, D. B. Hausman, M. J. Azain, and G. J. Hausman Pre- and Postnatal Dietary Conjugated Linoleic Acid Alters Adipose Development, Body Weight Gain and Body Composition in Sprague-Dawley Rats J. Nutr., October 1, 2001; 131(10): 2722 - 2731. [Abstract] [Full Text] [PDF]
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J. M. Brown, Y. D. Halvorsen, Y. R. Lea-Currie, C. Geigerman, and M. McIntosh Trans-10, Cis-12, But Not Cis-9, Trans-11, Conjugated Linoleic Acid Attenuates Lipogenesis in Primary Cultures of Stromal Vascular Cells from Human Adipose Tissue J. Nutr., September 1, 2001; 131(9): 2316 - 2321. [Abstract] [Full Text] [PDF]
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 Y.-P. Lu, Y.-R. Lou, Y. Lin, W. J. Shih, M.-T. Huang, C. S. Yang, and A. H. Conney Inhibitory Effects of Orally Administered Green Tea, Black Tea, and Caffeine on Skin Carcinogenesis in Mice Previously Treated with Ultraviolet B Light (High-Risk Mice): Relationship to Decreased Tissue Fat Cancer Res., July 1, 2001; 61(13): 5002 - 5009. [Abstract] [Full Text] [PDF]
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M. B. Sisk, D. B. Hausman, R. J. Martin, and M. J. Azain Dietary Conjugated Linoleic Acid Reduces Adiposity in Lean but Not Obese Zucker Rats J. Nutr., June 1, 2001; 131(6): 1668 - 1674. [Abstract] [Full Text]
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L. H. Baumgard, J. K. Sangster, and D. E. Bauman Milk Fat Synthesis in Dairy Cows Is Progressively Reduced by Increasing Supplemental Amounts of trans-10, cis-12 Conjugated Linoleic Acid (CLA) J. Nutr., June 1, 2001; 131(6): 1764 - 1769. [Abstract] [Full Text]
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J.W. Ryder, C.P. Portocarrero, X.M. Song, L. Cui, M. Yu, T. Combatsiaris, D. Galuska, D.E. Bauman, D.M. Barbano, M.J. Charron, et al. Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid: Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression Diabetes, May 1, 2001; 50(5): 1149 - 1157. [Abstract] [Full Text]
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